This present invention relates generally to depositing a thin metal coating onto the surface of implantable devices to achieve a more desirable device-tissue interface. More specifically, to a passive or non-reactive metallic coating incorporating one or more bioactive materials on the surface of an implantable device. And, more particularly, to electrochemically depositing a metallic coating incorporating one or more therapeutic agents onto a deformable structure for maintaining the patency of stenotic, occluded or diseased lumens post-implantation of the structure.
Implantable devices include, for example, stents, stent-grafts, embolic filters, detachable coils, pacemaker and defibrillator leads, plates, screws, spinal cages, dental implants, ventricular assist devices, artificial hearts, artificial heart valves, annuloplasty devices, artificial joints, and implantable sensors. Frequently, implanted medical apparatus must be designed to be sufficiently biocompatible to the host body. Otherwise, the body will manifest a rejection of the implant by way of a thrombotic, inflammatory or other deleterious response.
Such implantable devices, therefore, are designed or fabricated from materials possessing surface properties that minimize bodily response at the tissue-device interface. For example, stainless steel is a frequently used implant material due to the relatively passive oxide layer which forms on its surface. Moreover, much activity recently has been directed towards local delivery of bioactive materials into the target tissue via the device being implanted therein. Such bioactive materials are not limited to therapies for treating diseased or abnormal conditions, but also for minimizing the body's response to both the presence of and injury caused to the tissue during the implantation procedure.
These bioactive materials can include, without limitation, anti-inflammatory agents, anti-infective agents, anti-cancer agents, as well as agents used for vascular disease such as anti-restenosis compounds and anti-coagulant compounds. With regard to the latter, much research and development has been devoted to one particular implantable medical device for local delivery of bioactive compounds for treating vascular disease, more specifically, stents.
In recent years, intervention in the form of stenting has become widespread in the treatment of peripheral and coronary vascular disease. Stents are mechanical scaffolding devices typically used to maintain the patency of the previously occluded or stenosed vessel following or during percutaneous translumenal angioplasty (PTA) or percutaneous translumenal coronary angioplasty (PTCA). PTA or PTCA typically involves advancing a catheter, having an inflatable balloon on the distal end thereof, through a patient's arterial system until the balloon crosses an atherosclerotic lesion. The balloon is then inflated to dilate the artery. After dilation, the balloon is deflated and the catheter removed leaving an enlarged arterial passageway or lumen, thereby increasing blood flow. Following this procedure, a stent delivery system, which, in the instance of a balloon-expandable stent consists of a stent mounted on a similar balloon catheter or in the instance of a self-expanding stent consists of a stent loaded into the distal end of a delivery catheter, is advanced to the site, expanded and left in-situ to scaffold or prop-up the artery and maintain its patency. Alternatively, in certain procedures, the first step of pre-dilatation may be omitted in favor a direct stenting procedure whereby the stent delivery system dilates at the time of stenting. A significant number of PTA and PTCA procedures, however, result in a restenosis or re-narrowing of the lumen.
Re-narrowing or restenosis of the treated arteries, for example, occurs at a rate of 20% to 50% in patients undergoing this procedure, requiring repeat intervention either, for example, by further stenting, vascular grafting, debulking or bypass surgery. Any one individual's restenosis rate is dependent upon a number of morphological and clinical variables.
In addition to, and with respect to coronary artery intervention, the cellular response from angioplasty or stenting which, besides opening a previously occluded artery, also can cause fissuring of the atherosclerotc plaque and injury to resident arterial smooth muscle cells. In response to this injury, among other responses, hyperplasia, rapid proliferation, of smooth muscle cells occurs. Over a period of time, typically one to six months, this hyperplastic response can cause significant re-narrowing of the lumenal space opened by the intervention. For purposes of the instant invention, however, the lumen to be treated is not limited to coronary arteries, but also includes any other similar body conduit that tends to improperly constrict as a result of disease or malfunction, such as: arteries located within the mesentery, peripheral, or cerebral vasculature; veins; gastrointestinal tract; biliary tract; urethra; trachea; hepatic shunts; and fallopian tubes.
There are two general categories of stents, self-expanding stents and balloon-expandable stents. Self-expanding stents are typically made from nickel-titanium alloys, such as NITINOL, or stainless steel wire or wire braid. Such stents are typically compressed into a first shape and inserted into a sheath or cartridge positioned at the distal end of a delivery device. When the stent is positioned across the lesion, the sheath is withdrawn causing the stent to radially expand and abut the vessel wall. Balloon-expandable stents are typically introduced into a lumen on a catheter having an inflatable balloon on the distal end thereof. When the stent is at the desired location in the lumen, the balloon is inflated to circumferentially expand the stent. The balloon is then deflated and the catheter is withdrawn, leaving the circumferentially expanded stent in the lumen, usually as a permanent prosthesis for helping to hold the lumen open.
Attempts, both mechanical and pharmacological, to address restenosis include providing a suitable surface within the lumen for more controlled healing to occur in addition to the support provided by a stent. Mechanical attempts include providing a lining or covering in conjunction with a stent, a stent-graft. The covering of a stent-graft may prevent excessive tissue prolapse or protrusion of tissue growth through the interstices of the stent while allowing limited tissue in-growth to occur to enhance the implantation. The surface of the graft material at the same time prevents scarring from occluding the lumen and minimizes the contact between the fissured plaque and the hematological elements in the bloodstream. Both self-expanding and balloon-expandable stents can be used in conjunction with a covering or lining.
Pharmacological attempts have involved systemic delivery of drugs either orally, intravascularly or intramuscularly. And, more recently, drug eluting stents. These drug eluting stents typically involve a balloon-expandable stent modified to deliver anti-thrombotic or anti-restenotic compounds. Such devices typically involve the application of a coating, specifically adapted to hold and release drugs, to the surface of the stent. Many such coatings are polymers that perform such a hold and release function. These polymers can be degradeable, wherein the coating releases the drug via degradation of the polymer, or non-degradeable, whereby the drug diffuses therefrom into the surrounding environment.
These polymeric coatings, however, have certain limitations and shortcomings. In one regard, the degradation kinetics of polymers is often unpredictable. Consequently, it is difficult to predict how quickly a bioactive agent in a polymeric medium will be released. If a drug releases too quickly or too slowly from the polymeric medium, the intended therapeutic effect may not be achieved. In another aspect, in some instances, polymeric materials produce an inflammatory response. For example, certain polymeric coatings on stents have been observed to produce an inflammatory response, exascerbating restenosis. Moreover, yet another difficulty with polymers is their adherance to a substantially different substrate, such as a metal substrate, is difficult to achieve in manufacturing and to maintain after implantation. Mismatched properties such as different thermal and/or mechanical properties between the polymeric coating and the underlying substrate contribute to this difficulty.
Inadequate bonding or adhesion between a stent and an overlying polymeric coating may result in separation of these components over time, an undesirable characteristic for an implanted medical device to exhibit. Such separation is even more susceptible at areas of the stent subject to greater amounts of deflection during expansion, such as the apices or crowns of the stent.
Yet another limitation, is that it is difficult to evenly coat complex geometries and small objects not to mention small, complex metallic objects with a polymeric material. Therefore, small metallic objects, such as stents, become more difficult to coat evenly with a polymeric material. Yet a further limitation of polymer coatings is that they contribute bulk but do not contribute to the function of a stent which is to maintain lumen patency.
One proposed alternative to polymer coating is sintering. In such a sintering process, a heat and/or pressure treatment is used to weld small particles of metal to the surface of the structure. A porous metallic structure is created. Such sintered metallic structures, however, exhibit relatively large pores. When a bioactive material is loaded into the pores of a sintered metallic structure, the larger pore size can cause the biologically active material to release too quickly, possibly during delivery to the intended tissue. Also, because a high temperature is used to form a sintered structure, a bioactive material must be loaded into the sintered structure after the porous structure is formed. This method is not only time consuming, it is also difficult to impregnate the pores of the sintered structure with the biologically active material. Consequently, it is difficult to fully load the sintered structure with the bioactive material.
More recently, drug delivery from electrochemically deposited thin metal films has been posited. This coating process employs, as one of its steps, an electroless metal deposition. The drug to be delivered is dissolved or dispersed into a metalizing deposition bath, and is co-deposited on the implantable device. This deposition process involves the use of some heavy metals, such as stannous and palladium, to sensitize and activate the surface, which, albeit in small amounts, remains on the implantable device.